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KMID : 1204720180110020227
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International Journal of Stem Cells
2018 Volume.11 No. 2 p.227 ~ p.234
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The Pharmacological Inhibition of ERK5 Enhances Apoptosis in Acute Myeloid Leukemia Cells
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Kang Chang-Hee
Kim Jong-Soo
Kim C-Yoon
Kim Eun-Young
Chung Hyung-Min
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Abstract
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Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Extracellular signal-regulated kinase 5 (ERK5) plays a novel role in chemoresistance in some cancer cells and this pathway is a central mediator of cell survival and apoptotic regulation. The aim of this study was to investigate the effect of ERK5 inhibitor, XMD8-92, on proliferation and apoptosis in AML cell lines. Findings showed that XMD8-92 inhibited the activation of ERK5 by G-CSF and decreased the expression of c-Myc and Cyclin D1. The treatment of XMD8-92 reduced the phosphorylation of ERK5 leading to a distinct inhibition of cell proliferation and increased apoptosis in Kasumi-1 and HL-60 cells. Taken together, our study suggests that the inhibition of ERK5 by XMD8-92 can trigger apoptosis and inhibit proliferation in AMLs. Therefore, the inhibition of ERK5 may be an effective adjuvant in AML chemotherapy.
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KEYWORD
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ERK5, XMD8-92, Cell cycle, Apoptosis, Acute myeloid leukemia
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